Absorption, Distribution and Excretion
Male F344 rats (n=5 per group, 6 weeks old) were fed a diet containing 5% sodium isoascorbate for 22 weeks. During the study period, the total amount of isoascorbic acid in the rat urine was 203.3 ± 33.2 mg/100 mL, and the total amount of dehydroisoascorbic acid was 9.0 ± 5.1 mg/100 mL. Ascorbic acid and dehydroascorbic acid were not detected. The urine pH was 6.98 ± 0.31, which was significantly different from that of rats fed only a basal diet (6.31 ± 0.18; p < 0.05). Urine osmolality also differed significantly from the control group; the urine osmolality of rats given sodium isoascorbate was 1378 ± 277 mOsmol/kg H2O, while that of the control group was 1756 ± 200 mOsmol/kg H2O. Crystals were detected in the urine of rats fed a basal diet and sodium isoascorbate, or a basal diet alone. Metabolism/Metabolites Male F344 rats (n=5 per group, 6 weeks old) were fed a diet containing 5% sodium isoascorbate for 22 weeks. During the study, the rats excreted a total of 203.3 ± 33.2 mg/100 mL isoascorbic acid and 9.0 ± 5.1 mg/100 mL dehydroisoascorbic acid. Ascorbic acid and dehydroascorbic acid were not detected.

Toxicity Summary
Identification and Uses: Sodium isoascorbate forms white, free-flowing crystals. It is a synthetic antioxidant used in food and cosmetic formulations. Foliar application of sodium isoascorbate sprays and powders can be used to control senescence in citrus saplings and reduce ozone damage to Thompson seedless grapes. It is also used in hydraulic fracturing mixtures to prevent the precipitation of metal oxides (iron control). Human Exposure and Toxicity: Sodium isoascorbate does not cause chromosomal aberrations or sister chromatid exchanges in cultured human embryonic fibroblasts. Animal Studies: Application of sodium isoascorbate powder to intact and abraded skin in rabbits did not cause skin irritation. Instillation of sodium isoascorbate powder into the conjunctival sac of rabbits caused mild and transient conjunctival erythema, which subsided within 24 hours. During pregnancy, no maternal or fetal toxicity was observed in female rats and mice administered sodium isoascorbate orally by gavage at doses up to 1030 mg/kg/day. In a 13-week teratogenicity study, no developmental toxicity was observed in pregnant rats fed up to 5% sodium isoascorbate. Sodium isoascorbate was negative in the Ames test, host-mediated assay using Salmonella typhimurium, chromosomal aberration assay using Chinese hamster ovarian fibroblasts, dominant lethal assay in rats, and the Bacillus subtilis rec assay. However, sodium isoascorbate induced chromosomal aberrations in rat bone marrow cells in vivo. In vitro experiments showed that sodium isoascorbate did not increase the frequency of mitotic recombination in Saccharomyces cerevisiae D3 cells, nor did it induce heritable translocation heterozygosity in male mice. After 168 days of dietary supplementation with 5% sodium isoascorbate, rats did not exhibit morphological changes such as bladder mucosal hyperplasia. Dietary supplementation with up to 2.5% sodium isoascorbate did not promote the development of rare spontaneous tumors or cause benign tumors to transform into cancer. In a 24-week study, rats fed a diet containing 5% sodium isoascorbate developed simple hyperplasia of the bladder epithelium. Adding 1.25%–2.5% sodium isoascorbate to drinking water for 96 weeks did not significantly increase tumor incidence, tumor lethality, or tumor distribution in mice. It had no effect on stage II carcinomas of the non-glandular and glandular stomach, colon, liver, kidney, mammary gland, ear canal, or thyroid gland, but increased the incidence and average number of lesions in N-butyl-(4-hydroxybutyl)nitrosamine-induced bladder cancer. After administration of sodium isoascorbate to rats, it was excreted in the urine as isoascorbic acid and dehydroisoascorbic acid, but not ascorbic acid or dehydroascorbic acid. Ecotoxicity studies: Acute toxicity of sodium isoascorbate to the freshwater fish rainbow trout (Oncorhynchus myldss) was studied, showing a 96-hour LC50 greater than 100 mg/L (semi-static).

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Interactions
This study investigated the effects of 17 environmental chemicals on the development of bladder cancer in rats. Male F-344 rats were orally administered 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). The rats were fed diets containing 5% sodium saccharin, 2% sodium o-phenylphenolate (SOPP), 2% butylated hydroxyanisole (BHA), 5% sodium L-ascorbate (SA), 5% ascorbic acid, 5% ascorbic acid stearate, 5% sodium isoascorbate (SE), 0.8% ethoxyquinoline, 0.02% N-nitrosopyrrolidine, 0.2% methylhydroquinone, 0.2% hydroquinone, 0.2% resorcinol, 0.8% catechol, 0.5% pyrogallol, 0.6% carbazole, 0.1% quinoline, or 1% uric acid. The left ureter was ligated on day 22.
Animals were sacrificed and autopsied after week 24. The bladder, kidneys, ureters, and liver were stained for light microscopy. No cancer was induced in any rats. BBN induced papillary or nodular (PN) hyperplasia in 7% of control rats. The incidence and number of PN hyperplasia were significantly higher in BBN-treated rats fed sodium saccharin, SOPP, BHA, SA, SE, ethoxyquinoline, and carbazole than in the control group. Significant differences in the incidence and number of papillomas were also observed in BBN-treated rats fed sodium saccharin, SOPP, BHA, SA, and N-nitrosopyrrolidine. Histopathological changes were observed in the left kidney, with more common dilatation of the left pelvis and ureter. No abnormalities were observed in the right kidney, ureter, and liver. The authors conclude that the ureteral ligation system appears suitable as a short-term screening method for bladder carcinogens and tumor promoters. The carcinogenic activity of butylated hydroxyanisole (BHA) in rats, mice, and hamsters was investigated, along with the effects of antioxidants BHA, butylated hydroxytoluene (BHT), ethoxyquinoline (EQ), sodium L-ascorbate (SA), ascorbic acid (AA), sodium isoascorbate (SE), propyl gallate (PG), and α-tocopherol on two-stage chemical carcinogenesis in rats. This carcinogenesis was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 1,2-dimethylhydrazine (DMH), diethylnitrosamine (DEN), 7,12-dimethylbenzanthracene (DMBA), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), N-ethyl-N-hydroxyethylnitrosamine (EHEN), or N-methylnitrosourea (MNU). BHA significantly induced squamous cell carcinoma in the forestomach of rats and hamsters. The carcinogenic effect of crude BHA on the forestomach is mainly attributed to 3-tert-butylnitrosamine (3-tert-BHA). In a two-stage chemical carcinogenesis model, BHA promoted the development of MNNG or MNU-induced forestomach cancer and BBN or MNU-induced bladder cancer, and inhibited the development of DEN or EHEN-induced liver cancer and DMBA-induced breast cancer. BHT showed the potential to promote bladder cancer and MNU-induced thyroid cancer, and inhibited DMBA-induced ototrichum carcinoma. EQ promoted the development of EHEN-induced renal cancer and inhibited DMBA-induced breast cancer and EHEN-induced liver cancer. SA promoted the development of forestomach and bladder cancer, and SE similarly enhanced the development of bladder cancer. α-Tocopherol inhibited the development of ototrichum carcinoma. No antioxidants were found to have any effect on the development of adenogastric cancer. The results clearly demonstrate that the effects (promoting or inhibiting) of antioxidants vary depending on the organ studied, highlighting the importance of a holistic approach to antioxidant research. This study investigated the carcinogenic activity of butylated hydroxyanisole (BHA) in rats and hamsters. To obtain information about the mechanism of action of BHA on the forestomach, the following aspects were investigated: the effects of 12 BHA-related phenolic compounds on the hamster forestomach; the effects of BHA combined with other antioxidants on the rat forestomach; and the metabolism of BHA in the forestomach. Furthermore, the effects of several antioxidants on two-stage carcinogenicity in rats were investigated. Squamous cell carcinoma was induced in the forestomach of rats and hamsters fed BHA. In a small study, squamous cell carcinoma developed in 1 out of 13 hamsters. The tumorigenic effect of crude BHA on the forestomach was mainly attributed to the action of 3-tert-butylBHA. p-tert-butylphenol and 2-tert-butyl-4-methylphenol induced significant hyperplasia and papillomas in the hamster forestomach. BHA and other antioxidants, particularly propyl gallate and ethoxyquin, exhibited an additive effect in inducing forestomach hyperplasia and cytotoxicity. Although small amounts of metabolites were detected in gastric contents, BHA or its metabolites were not found in the forestomach epithelium. Therefore, BHA itself or its metabolites generated from interactions with gastric juice may have a direct effect on the gastric epithelium. BHA enhanced forestomach carcinogenesis in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine or N-methylnitrosourea (MNU) and enhanced bladder carcinogenesis induced by MNU or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Conversely, it inhibited liver carcinogenesis induced by diethylnitrosamine or N-ethyl-N-hydroxyethylnitrosamine (EHEN) and breast cancer induced by 7,12-dimethylbenzo[a]anthracene (DMBA). BHT promoted BBN- or MNU-induced bladder cancer and MNU-induced thyroid cancer, but inhibited DMBA-induced ototubular cancer. Ethoxyquinoline promoted EHEN-induced kidney cancer but inhibited DMBA-induced breast cancer and EHEN-induced liver cancer. Sodium ascorbate promoted forestomach and bladder cancer, and isoascorbate also enhanced bladder cancer. α-Tocopherol inhibited ototubular cancer. None of the tested antioxidants had any effect on the development of adenogastric cancer. Therefore, antioxidants have independent regulatory (promoting or inhibiting) effects in different organs. The regulatory effects of antioxidants were examined in the carcinogenic system after treatment with N,N-dibutylnitrosamine. Male F344 rats were fed a basal diet containing 2% butylated hydroxyanisole (BHA), 1% butylated hydroxytoluene (BHT, containing 7 ppm vitamin K), 0.8% ethoxyquinoline, 5% sodium L-ascorbate, 5% sodium isoascorbate, or no added chemicals for 32 weeks after 4 weeks of drinking water supplementation with 0.05% N,N-dibutylnitrosamine. BHA promoted the development of forestomach cancer but not esophageal cancer. BHT promoted esophageal cancer but not forestomach cancer. Ethoxyquinoline significantly promoted esophageal tumorigenesis. Other evaluated antioxidants had no effect on the development of esophageal or forestomach cancer. BHA significantly increased DNA synthesis in forestomach epithelial cells, while BHT tended to increase DNA synthesis in esophageal epithelial cells. Therefore, BHA and BHT exhibited different modifying responses in the development of esophageal and forestomach cancers. For more complete data on interactions of sodium isoascorbate (7 types in total), please visit the HSDB record page. Non-human toxicity values: Oral LD50 in rats > 5 g/kg

nearly odorless, fluffy white to off-white crystalline powder. Used as an antioxidant and preservative.
See also: Sodium isoascorbate (note moved to).

C6H7NAO6

198.1060

198.014

6381-77-7

Erythorbic acid;89-65-6

54680695

Light yellow to yellow solid powder

1.954g/cm3

552.7ºC at 760mmHg

168 - 170ºC

238.2ºC

3

6

2

13

237

2

C([C@H]([C@@H]1C(=C(C(=O)O1)O)O)O)[O-].[Na+]

RBWSWDPRDBEWCR-RKJRWTFHSA-N

InChI=1S/C6H7O6.Na/c7-1-2(8)5-3(9)4(10)6(11)12-5;/h2,5,8-10H,1H2;/q-1;+1/t2-,5-;/m1./s1

sodium;(2R)-2-[(2R)-3,4-dihydroxy-5-oxo-2H-furan-2-yl]-2-hydroxyethanolate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~252.39 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)